Global view of enhancer-promoter interactome in human cells

Proc Natl Acad Sci U S A. 2014 May 27;111(21):E2191-9. doi: 10.1073/pnas.1320308111. Epub 2014 May 12.

Abstract

Enhancer mapping has been greatly facilitated by various genomic marks associated with it. However, little is available in our toolbox to link enhancers with their target promoters, hampering mechanistic understanding of enhancer-promoter (EP) interaction. We develop and characterize multiple genomic features for distinguishing true EP pairs from noninteracting pairs. We integrate these features into a probabilistic predictor for EP interactions. Multiple validation experiments demonstrate a significant improvement over state-of-the-art approaches. Systematic analyses of EP interactions across 12 cell types reveal several global features of EP interactions: (i) a larger fraction of EP interactions are cell type specific than enhancers; (ii) promoters controlled by multiple enhancers have higher tissue specificity, but the regulating enhancers are less conserved; (iii) cohesin plays a role in mediating tissue-specific EP interactions via chromatin looping in a CTCF-independent manner. Our approach presents a systematic and effective strategy to decipher the mechanisms underlying EP communication.

Keywords: 3C; bioinformatics; chromatin interaction; gene regulation; genomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Computational Biology
  • Computer Simulation
  • Enhancer Elements, Genetic / genetics
  • Enhancer Elements, Genetic / physiology*
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Genomics / methods
  • Humans
  • Models, Genetic*
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / physiology*
  • Signal Transduction / physiology*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • cohesins